Polyubiquitylation drives replisome disassembly at the termination of DNA replication
Polyubiquitylation drives replisome disassembly at the termination of DNA replication
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DOI：
10.1126/science.1253585
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发表时间：
2014-10-24
期刊：
影响因子：
56.9
通讯作者：
Gambus, Agnieszka
中科院分区：
文献类型：
--
作者：
Moreno, Sara Priego;Bailey, Rachael;Gambus, Agnieszka
在DNA复制终止过程中，复制叉的解析对于真核生物基因组的准确复制至关重要。在这里，我们提出的证据一致的想法，复制体组件（Mcm 7）的polyubiquitylation导致其解体的收敛终止叉，因为p97/VCP/Cdc 48蛋白质重塑的行动。使用非洲爪蟾卵提取物，我们已经表明，阻断polyubiquitylation的结果在延长协会的活性解旋酶与复制染色质。Mcm 7亚基是我们发现在复制终止过程中聚泛素化的活性解旋酶的唯一组成部分。所观察到的多泛素化之后是依赖于p97/VCP/Cdc 48的活性解旋酶的分解。总之，我们的数据提供了深入了解的机制，在真核DNA复制终止的复制体解体。
Resolution of replication forks during termination of DNA replication is essential for accurate duplication of eukaryotic genomes. Here we present evidence consistent with the idea that polyubiquitylation of a replisome component (Mcm7) leads to its disassembly at the converging terminating forks because of the action of the p97/VCP/Cdc48 protein remodeler. Using Xenopus laevis egg extract, we have shown that blocking polyubiquitylation results in the prolonged association of the active helicase with replicating chromatin. The Mcm7 subunit is the only component of the active helicase that we find polyubiquitylated during replication termination. The observed polyubiquitylation is followed by disassembly of the active helicase dependent on p97/VCP/Cdc48. Altogether, our data provide insight into the mechanism of replisome disassembly during eukaryotic DNA replication termination.